The mechanism by which virulent viruses inhibit cellular protein synthesis is not understood. For vesicular stomatitis virus to inhibit cellular protein synthesis, the expression of three of the five genes specificied by the virus is necessary---those coding for proteins N, NS and L. This conclusion was arrived at by examining the ability of various temperature sensitive mutants of vesicular stomatitis virus to inhibit cellular protein synthesis at the non-permissive temperature. Further studies using ultraviolet irradiated vesicular stomatitis virus to infect L cells have led to the conclusions that (1) N and NS proteins must be newly transcribed and synthesized and (2) minimally functional virion L protein is sufficient (in addition to newly synthesized N and NS proteins) for expression of protein synthesis inhibition. Even at very high multiplicities of infection virion N and NS proteins were unable to inhibit cellular protein synthesis. The role of these viral proteins in host protein synthesis inhibition is not known. Our studies using temperature sensitive mutants of vesicular stomatitis virus indicate that proteins L, N, and NS must be minimally functional, suggesting that some product of their reaction may be actually responsible for protein synthesis inhibition. These products are involved in both primary and secondary transcription. Mutants ts G41 and W10 (group IV) differ in that W10 is capable of protein synthesis inhibition whereas G41 is not. Comparative studies of the RNA products synthesized by these mutants will be carried out to see if any differences occur, accounting for inhibition. BIBLIOGRAPHIC REFERENCES: Abreu, S. L., Lucas-Lenard. 1977. Inhibition of Cellular and Viral Protein Synthesis by 3-Methylneoxindole. Antimicrob. Agents and Chemother. 11-521-527. Marvaldi, J. L., J. Lucas-Lenard, M. J. Sekellick, and P. M. Marcus. 1977. Cell Killing by Viruses. IV. Cell Killing and Protein Synthesis Inhibition by Vesicular Stomatitis Virus Require the Same Gene Functions. Virology 79, In press.